POS0636 SHOULD COMPLETE B-CELL DEPLETION BE SUSTAINED IN RITUXIMAB LONG-TERM TREATED PATIENTS FOR RHEUMATOID ARTHRITIS?
Authors: R. Ghossan, O. Al Tabaa, A. Combier, A. Steelandt, M. Thomas, C. Miceli Richard, A. Moltó, Y. Allanore, J. Avouac
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Complete peripheral B cell depletion has been considered as a relevant indicator of short-term response to rituximab (RTX) in rheumatoid arthritis (RA) [1,2]. However, no information is available to validate this observation in RA patients long-term treated with RTX. <h3>Objectives</h3> To determine whether sustained complete B cell (BC) depletion is associated with a better clinical response in RA patients long-term treated with RTX. <h3>Methods</h3> Retrospective routine care study conducted in the Rheumatology department of Cochin hospital. We included consecutive patients fulfilling the ACR/EULAR 2010 classification criteria for RA hospitalized in 2021 for a new RTX infusion. All recruited patients had received at least 3 prior RTX infusions and had disease activity assessment (DAS28 and DAS28-CRP) and CD19 counts (Aquios, Beckman Coulter) available during each of the 4 last infusion visits. The primary endpoint was the course of DAS28 and DAS28-CRP, calculated the day of the last 4 infusion visits according to sustained complete (mean CD19 counts &lt;18/µL) or incomplete (mean CD19 counts ≥18/µL) BC depletion. Secondary endpoints were the frequency of end-of-dose effect and patient self-reported RA flares at each infusion visit, as well as the course of pain/fatigue VAS, CRP and gammaglobulin levels according to complete or incomplete B cell depletion. <h3>Results</h3> We included 126 patients (105 women, 83%) with a mean age of 64±12 years and a mean disease duration of 22± 5 years. Only 43 patients (34%) had maintained complete BC depletion during the last 4 infusions (mean CD19 counts 13±4/µL) (<b>Figure 1A-B</b>). Patients with incomplete BC depletion (n=83, mean CD19 counts: 77±73/µL, p&lt;0.001) did not differ from those who maintained complete BC depletion in terms of age, gender, disease duration, structural damages and concomitant treatment. Patients with incomplete BC depletion had a higher frequency of rheumatoid factor (92% vs. 77%, p=0.018) and ACPA (84% vs. 72%, p=0.11); these patients had received RTX for a longer period (99±57 months vs. 69±47 months, p=0.003), with significantly higher number of infusions (14±7 vs. 12±6 infusions, p=0.037) and increased cumulative dose (10±6 g vs. 8±5 g, p=0.10) compared to patients with sustained complete BC depletion. On the other hand, their interval between 2 infusions was significantly longer (8±3 months vs. 6±1 months, p&lt;0.001). The course of DAS28 and DAS28-CRP during the last 4 infusions was not different between the 2 groups (<b>Figures 1C-D</b>). The mean DAS28 and DAS28-CRP calculated at the time of last 4 infusion visits did not differ between patients with incomplete or sustained complete BC depletion (DAS28: 2.71±1.06 vs. 3.01±1.10, p=0.33 and DAS28-CRP: 2.53±0.88 vs. 2.88±0.84, p=0.095). The frequency of an end-of-dose effect and self-reported flares was similar between the 2 groups, as well as the evaluation of pain VAS, asthenia VAS, CRP and gammaglobulin levels (<b>Figures 1E-H</b>). <h3>Conclusion</h3> Maintaining complete BC depletion is not a therapeutic target to achieve in RA patients in long-term maintenance therapy with RTX. These results show that it is possible to space out RTX infusions to 8 months without loss of clinical benefit, which remains identical to that of patients treated every 6 months with sustained BC depletion. This result may have clinical implications during the COVID-19 pandemic since the antibody response to SARS-CoV-2 vaccination is preferentially obtained in patients with detectable B cells [3]. <h3>References</h3> [1]Vital EM et al. Arthritis Rheum 2011;63:603–8. [2]Dass S et al. Arthritis Rheum 2008; 58(10):2993–2999. [3]Avouac et al, Rheumatology 2022 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.